The present invention relates in general to the field of biological tissue repair. More particularly, it concerns a new light activated device, which can be used for improved wound closure.
The conventional methods for tissue repair use sutures, staples or clips [Werker 1997]. Sutures are favored because they are cost effective, reliable and more importantly, are suitable for almost any type of tissue. The use of any of these conventional fasteners, however, causes tissue injury due to their mechanical intrusion. By their very nature, they result in a xe2x80x9cforeign bodyxe2x80x9d being left in the tissue. Tissue injury and foreign body reaction can give rise to such problems as inflammation, granuloma formation, scarring, and stenosis. Sutures become difficult or tedious to execute in microsurgical or minimally invasive endoscopic applications, where staples or clips are better suited. Staples and clips are not easily adapted to different tissue dimensions, however, and maintaining precision of alignment of the tissue is difficult because of the relatively large force required to fit them. Finally, none of these fasteners produce a watertight seal over the repair.
Laser welding is another technique used to achieve tissue anastomosis. Laser energy is used to induce thermal changes in connective tissue proteins. As temperatures rise and/or heating times are prolonged, cellular and tissue structural proteins undergo denaturation and conformational changes, a process defined as coagulation [Pearce 1995]. This process results in the joining or bonding of the adjoining tissue edges [Schober 1986, Bass 1992]. A wide range of lasers have been used for laser tissue welding. Infrared sources include carbon dioxide (CO2), thulium-holmium-chromium, holmium, thulium and neodymium rare earth doped garnets (THC:YAG,Ho:YAG, Tm:YAG or Nd:YAG), and gallium aluminium arsenide diode (GaAlAs) lasers. Visible sources include potassium-titanyl-phosphate (KTP) frequency-doubled Nd:YAG and argon lasers. The laser energy is absorbed by water at the infrared wavelengths and by hemoglobin and melanin at the visible wavelengths, thereby heating proteins within the target tissue.
Compared with conventional tissue repair techniques, the laser welding technique offers reduced suture and needle trauma [Godlewski 1996], reduced foreign body reaction [Dalsing 1992], reduced bleeding [Chikamatsu 1995], the potential to form an immediate watertight anastomosis intraoperatively [Bass 1995] and shorter operating times [Maragh 1988]. While some success has been achieved in experimental applications, clinical use of this technology has been hindered by unreliable fusion strength [Jain 1979, Grubbs 1988], excessive thermal damage of tissue caused by direct laser heating [Thomsen 1985, Kopchok 1988, Chow 1990], technical difficulties with tissue alignment [Bass 1995], the ambiguity of the end point for the procedure [Bass 1995], and by poor reproducibility [Thomsen 1995].
Laser soldering using protein based biological glues and other compounds is another tissue repair technique that may provide greater bond strength and lesser collateral thermal damage with a greater tolerance of variations in laser parameters. Useful solders include blood [Krueger 1985, Wang 1988], cryoprecipitate [Grubbs 1988, Cikrit 1990], and albumin [Poppas 1988, Bass 1993, Poppas 1993]. Wavelength-specific chromophores (dyes) are often added to the solders to provide for differential absorption between the dyed region and the surrounding tissue. One advantage of the laser soldering technique is that the area may be bathed by the laser radiation while energy is absorbed selectively only by the target. Hence, the requirement for precise focussing and aiming of the laser beam may be removed. Furthermore, due to the increased absorption characteristics of the dyed tissue, lower laser irradiances may be used to achieve the required effect, and thus, the safety of the technique is increased. Examples of such dyes include carbon black, Fen 6, indocyanine green and fluorescein.
The use of synthetic polymers as a scaffold for protein solders provides a new device, which may be tailored to a wide range of clinically relevant geometries for tissue repair. The features of the novel solder-doped polymeric scaffolds of the present invention greatly improve the clinical applicability of laser tissue repair. For example, problems associated with inflexibility in conforming to various tissue geometries, instability in a hydrated environment due to non-uniform tissue adhesive denaturation, and solubility in physiological fluids prior to denaturation are overcome using the new materials of this invention. The materials and methods described herein offer a viable alternative to conventional fasteners, including sutures, staples and clips, currently used for tissue repair. In addition, the present invention permits the use of patches prepared from the solder-doped polymeric scaffolds in the field, thereby providing a simple and effective method to stop bleeding and repair tissue quickly in an emergency situation.
Polymer scaffolds are fabricated with synthetic materials including, but not limited to, poly(L-lactic acid) (PLA), poly(glycolic acid) (PGA), poly(L-lactic-co-glycolic acid) PLGA, poly(.epsilon.-caprolactone), polyortho esters, polyanhydrides and poly glycerol (PEG), using a solvent-casting and particulate-leaching technique. The scaffold forms a platform for the protein solder that is composed of such materials as, but not limited to, serum albumin, collagen and fibrinogen. A chromophoric dye such as indocyanine green (ICG) or carbon black may be added to the solder to selectively absorb the laser irradiation. The end result is a device, which can be light activated and used to join tissue together.
The polymeric scaffold described herein is designed to mimic the body""s own extracellular matrix [Mikos 1994]. Furthermore, the present invention provides a porous network into which traditional protein solders are readily absorbed, and degrades as need for the support diminishes. The solder, the polymer scaffolds and the chromophoric dye are biocompatible, and thus, foreign body reaction and infection are expected to be minimal. In fact, polylactic acid-based polymers are commercially available, and already have FDA approval for clinical procedures. Upon activation with a laser, the solder-doped scaffolds tend to undergo a small amount of shrinkage. This shrinkage helps to maintain edge-alignment as the tissue edges are gently pulled together. In addition, slight-rehydration of the solder-doped polymer scaffolds upon application to the tissue assists with tissue apposition, thus relieving the need for excessive stay-sutures often associated with laser tissue repair techniques. Various dopants including, hemostatic and thrombogenic agents, antibiotics, anesthetics, and various growth factors may be added to the solder-doped polymer scaffolds to assist in the wound healing process.
The present inventors recognized that there are three primary disadvantages of previously described solders. First, application of such solders to the repair site can be difficult. Liquid protein solders suffer from problems associated with xe2x80x9crunawayxe2x80x9d of the low viscosity material [McNally 1999a, McNally 1999b, McNally 1999e]. Solid protein solders, while offering improved repair strength over liquid solders, are brittle and inflexible, and thus, not easily adapted to different tissue geometries [McNally 1999d, McNally 1999e, McNally 1999f]. Second, more energy is generally absorbed near the upper portion of the solder, which is closer to the laser source, regardless of whether water or an absorbing dye is used as the chromophore. Irradiation of the solder produces a temperature gradient over the depth of the solder. The gradient is a function of the irradiance and the absorption coefficient, xcexca, of the solder/dye combination. The 1/e penetration depth of the laser light is defined as 1/xcexca, neglecting scattering. FIG. 1 shows a plot of the optical penetration depth of laser light at 805 nm in albumin protein solders containing different concentrations of ICG dye. The optical penetration depth is observed to decrease with increased ICG dye concentration. Depending on the temperature gradient and the laser exposure, the upper portion of the solder can become over-coagulated while the most critical regionxe2x80x94the solder/tissue interfacexe2x80x94remains uncoagulated. Non-uniform denaturation across the solder thickness can result in the formation of an unstable solder-tissue bond [McNally 1999b, Chan 1997]. Third, the protein solder is soluble in physiological solutions prior to laser irradiation, which can be problematic during application. In addition, as these solders are often subjected to blood dilution during operation, the solder may undergo mechanical alteration that can weaken the solder-tissue repair [Lauto 1998].
More particularly, the present invention includes a composition suitable for the repair of separated biological tissue using a biodegradable polymer that is impregnated with a solder that is biologically compatible and a chromophoric dye that enhances the amount of light energy that the composition will absorb.
The present invention also includes a method for the application of the biodegradable polymer containing the weldable material and chromophoric dye to biological tissue and affixing it there by application of laser light. The steps in the method are placing the pieces of separated biological tissue, if they are completely separated, in proximity close to one another approximating their normal relationship with one another; placing the polymeric biodegradable scaffold containing the solder material and the chromophoric dye over, around or in the wound of the biological tissue in a manner that will allow the wound to be sealed after the composition is exposed to laser light; and exposing the polymeric material containing the solder and the chromophoric dye to a laser light in order to cause the adhesion of the solder and the polymer scaffold to the biological tissue.
In summary, the present invention includes a composition suitable for the repair of separated biological tissue using a biodegradable polymer that is impregnated with a solder that is biologically compatible and a chromophoric dye that enhances the amount of light energy that the composition will absorb.